Safety and Efficacy of Multiple Doses of Canakinumab (ACZ885) in Chronic Obstructive Pulmonary Disease (COPD) Patients

• ClinicalTrials.gov Identifier: NCT00581945
• Recruitment Status: Completed
• First Posted: December 28, 2007
• Results First Posted: June 27, 2011
• Last Update Posted: June 30, 2011
• Sponsor: Novartis
• Information provided by: Novartis

Study Description

Brief Summary:

Was to evaluate the safety, tolerability and efficacy of multiple doses of canakinumab (ACZ885) vs. placebo when administered via intravenous infusion (IV), on pulmonary function in patients with COPD

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Canakinumab; Drug: Placebo	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 147 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Randomized, Double-blind, Placebo Controlled, Exploratory Study to Assess the Safety and Efficacy of Multiple Doses of ACZ885 in Chronic Obstructive Pulmonary Disease (COPD) Patients
• Study Start Date: January 2007
• Actual Primary Completion Date: May 2010
• Actual Study Completion Date: May 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Canakinumab; Participants received an initial dose of 1 mg/kg canakinumab (ACZ885) via intravenous infusion. Four weeks later, participants received a dose of 3 mg/kg canakinumab, and another dose of 3 mg/kg two weeks later. Thereafter, participants received doses of 6 mg/kg every four weeks until completion of the 45-week treatment period.	Drug: Canakinumab; The dose of canakinumab (ACZ885) administered was individualized, based on the subject's weight pre-dose, and was administered via intravenous infusion.
Placebo Comparator: Placebo; Participants received a matching placebo intravenous infusion at weeks 1, 5, 7, and thereafter every four weeks until completion of the 45-week treatment period.	Drug: Placebo; Matching placebo to ACZ885 administered via intravenous infusion.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: Baseline, Week 25 and Week 45 ]
   Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. FEV1 was measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation. All spirometry calibrations and evaluations followed the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. A positive change from baseline in FEV1 indicates improvement in lung function.
2. Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted [ Time Frame: Baseline, Week 25 and Week 45 ]
   The FEV1 percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 % predicted indicates improvement in lung function.
3. Change From Baseline in Forced Vital Capacity (FVC) [ Time Frame: Baseline, Week 25 and Week 45 ]
   Forced Vital Capacity is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed by spirometry. A positive change from baseline in FVC indicates improvement in lung function.
4. Change From Baseline in Slow Vital Capacity (SVC) [ Time Frame: Baseline, Week 25 and Week 45 ]
   Vital Capacity is the amount of air that can be forcibly exhaled from the lungs after a full inhalation. Slow Vital Capacity (SVC) test is performed by having the patient slowly and completely blow out all of the air from their lungs. A positive change from baseline in SVC indicates improvement in lung function.
5. Change From Baseline in Forced Expiratory Flow 25% to 75% [ Time Frame: Baseline, Week 25 and Week 45 ]
   The forced expiratory flow (FEF) 25%-75% measurement describes the amount of air expelled from the lungs during the middle half (25% - 75%) of the forced vital capacity test and is measured using spirometry. A positive change from baseline in FEF indicates improvement in lung function.

Secondary Outcome Measures :

1. Number of Participants Who Experienced Serious Adverse Events or Discontinued Due to Adverse Events [ Time Frame: Adverse events were collected during the 45 week treatment period and the 12 week follow-up period. ]
   Safety was assessed by the number of participants with serious adverse events and/or adverse events leading to study discontinuation. A summary of adverse events is presented with this outcome, additional details are provided in the Adverse Events section.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male and/or female subjects from 40-80 years (inclusive) of age
• Subjects have a clinical diagnosis of COPD
• Smokers or Ex-smokers with a smoking history of at least 20 pack years
• Post-bronchodilator forced expiratory volume in 1 second (FEV1 ) at screening ≤ 50% of the predicted normal value
• Post-bronchodilator FEV1/FVC ratio < 70%
• History of at least one treated exacerbation during the 24 months year prior to screening or C-Reactive Protein (CRP) ≥3.47 mg/L,
• Subjects should have no concomitant other lung disease or significant concomitant medical conditions that would affect the subjects' safety when participating in the study, or that would be expected to impact on the results of the study
• Female subjects must have been surgically sterilized at least 6 months prior to screening or must be using two forms of contraception, or postmenopausal women
• Able to provide written informed consent prior to study participation.
• Able to communicate well with the investigator and comply with the requirements of the study.

Exclusion Criteria:

• COPD exacerbation(s) requiring treatment within 4 weeks prior to first dosing
• History of lung reduction surgery
• Any undiagnosed nodule on chest x-ray
• Presence of certain medical conditions as specified by the protocol
• Subjects requiring oral or parenteral corticosteroids equivalent to > 10 mg/day or > 20 mg every other day of prednisone or prednisolone
• Documented homozygous alpha-1 antitrypsin deficiency.
• Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.
• Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
• A past medical history of clinically significant electrocardiogram (ECG) abnormalities or a family history of a prolonged QT-interval syndrome.
• A known hypersensitivity to drugs similar to the study drug.
• History of immunocompromise, including a positive HIV test result.
• A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
• History of drug or alcohol abuse within the 12 months prior to screening or evidence of such abuse as indicated by the laboratory assays conducted during screening.

Contacts and Locations

Locations

United States, California

Novartis Investigator Site

Anaheim, California, United States, 92801

Novartis Investigator Site

Los Angeles, California, United States, 90095

United States, Florida

Novartis Investigator Site

Panama City, Florida, United States, 32405

United States, Georgia

Novartis Investigator Site

Marietta, Georgia, United States, 300060

United States, Maryland

Novartis Investigator Site

Baltimore, Maryland, United States, 21224

United States, Michigan

Novartis Investigator Site

Livonia, Michigan, United States, 48152

United States, Minnesota

Novartis Investigator Site

Minneapolis, Minnesota, United States, 55402

United States, Nebraska

Novartis Investigator Site

Omaha, Nebraska, United States, 68198-5885

United States, New York

Novartis Investigator Site

Buffalo, New York, United States, 14215

United States, South Carolina

Novartis Investigator Site

Spartanburg, South Carolina, United States, 29303

United States, Virginia

Novartis Investigator Site

Richmond, Virginia, United States, 23225

Sponsors and Collaborators

Novartis

Investigators

• Principal Investigator: NOVARTIS; Novartis investigator site

More Information

• Responsible Party: External Affairs, Novartis
• ClinicalTrials.gov Identifier: NCT00581945
• Other Study ID Numbers: CACZ885B2204
• First Posted: December 28, 2007
• Results First Posted: June 27, 2011
• Last Update Posted: June 30, 2011
• Last Verified: June 2011

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases